Phillip R Purnell1, Benjamin L Addicks1, Habib G Zalzal1, Scott Shapiro1, Sijin Wen2, Hassan H Ramadan1, Vincent Setola3,4,5, David P Siderovski6. 1. Department of Otolaryngology, Head and Neck Surgery, West Virginia University School of Medicine, Morgantown, West Virginia, USA. 2. Department of Biostatistics, West Virginia University School of Public Health, Morgantown, West Virginia, USA. 3. Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia, USA. 4. Department of Neuroscience, West Virginia University School of Medicine, Morgantown, West Virginia, USA. 5. Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, Morgantown, West Virginia, USA. 6. Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia, USA, dsiderov@gmail.com.
Abstract
BACKGROUND: Chronic rhinosinusitis (CRS) is a multifaceted disease with a significant genetic component. The importance of taste receptor signaling has recently been highlighted in CRS; single nucleotide polymorphisms (SNPs) of bitter tastant-responsive G-protein-coupled receptors have been linked with CRS and with altered innate immune responses to multiple bacterially derived signals. OBJECTIVE: To determine in CRS the frequency of six SNPs in genes with known bitter tastant signaling function. METHODS: Genomic DNA was isolated from 74 CRS volunteers in West Virginia, and allele frequency was determined and compared with demographically matched data from the 1,000 Genomes database. RESULTS: For two SNPs in a gene recently associated with bitterant signaling regulation, RGS21, there were no associations with CRS (although the frequency of the minor allele of RGS21, rs7528947, was seen to increase with increasing Lund-Mackay CT staging score). Two TAS2R bitter taste receptor gene variants (TAS2R19 rs10772420 and TAS2R38 rs713598), identified in prior CRS genetics studies, were found to have similar associations in this study. CONCLUSION: Unique to our study is the establishment of an association between CRS in this patient population and GNB3 SNP rs5443, a variation in an established G protein component downstream of bitterant receptor signal transduction.
BACKGROUND:Chronic rhinosinusitis (CRS) is a multifaceted disease with a significant genetic component. The importance of taste receptor signaling has recently been highlighted in CRS; single nucleotide polymorphisms (SNPs) of bitter tastant-responsive G-protein-coupled receptors have been linked with CRS and with altered innate immune responses to multiple bacterially derived signals. OBJECTIVE: To determine in CRS the frequency of six SNPs in genes with known bitter tastant signaling function. METHODS: Genomic DNA was isolated from 74 CRS volunteers in West Virginia, and allele frequency was determined and compared with demographically matched data from the 1,000 Genomes database. RESULTS: For two SNPs in a gene recently associated with bitterant signaling regulation, RGS21, there were no associations with CRS (although the frequency of the minor allele of RGS21, rs7528947, was seen to increase with increasing Lund-Mackay CT staging score). Two TAS2R bitter taste receptor gene variants (TAS2R19rs10772420 and TAS2R38 rs713598), identified in prior CRS genetics studies, were found to have similar associations in this study. CONCLUSION: Unique to our study is the establishment of an association between CRS in this patient population and GNB3 SNP rs5443, a variation in an established G protein component downstream of bitterant receptor signal transduction.
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